Evaluation of general behavior, memory, learning performance, and brain sexual differentiation in F1 offspring males of rats treated with flutamide during late gestation

Journal of Toxicological Sciences

Volumn 30, Issue 3, 2005, Pages 249-259

  Goto, Kazunori ^a   Koizumi, Keiji ^a   Ohta, Yoshio ^a   Hashi, Mariko ^a   Fujii, Yoshinobu ^a   Ohbo, Nanae ^a   Saika, Osamu ^a   Suzuki, Hiroetsu ^b   Saito, Kenichi ^b   Suzuki, Katsushi ^b  

^a NIPPON SODA CO LTD   (Japan)

^b NIPPON VETERINARY AND LIFE SCIENCE UNIVERSITY   (Japan)

Author keywords

Anti androgen; Brain sexual differentiation; Flutamide; General behavior; Learning performance; Rats

Indexed keywords

ANDROGEN RECEPTOR; FLUTAMIDE; MESSENGER RNA; TESTOSTERONE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BEHAVIOR; CONTROLLED STUDY; CORRELATION ANALYSIS; DOT HYBRIDIZATION; FEMALE; HIPPOCAMPUS; HYPOTHALAMUS; LEARNING; MALE; MEMORY; MOTOR ACTIVITY; NONHUMAN; PERCEPTION; PREGNANCY; PREOPTIC AREA; PROGENY; PROSTATE; RAT; SEX DIFFERENCE; SEX DIFFERENTIATION; SIGNAL TRANSDUCTION; STATISTICAL SIGNIFICANCE;

ANIMALIA;

EID: 24944570642     PISSN: 03881350     EISSN: 18803989     Source Type: Journal    
DOI: 10.2131/jts.30.249     Document Type: Article

References (46)

1. Arai, Y., Sekine, Y. and Murakami, S. (1996): Estrogen and apoptosis in the developing sexually dimorphic area in female rats. Neurosci. Res., 25, 403-407.
2. Bartlett, M.S. (1937): Properties of sufficiency and statistical tests. Proc. Roy. Soc., A160, 268-282.
3. Brand, T. and Slob, A.K. (1991): Perinatal flutamide and mounting and lordosis behavior in adult female Wistar and Sprague-Dawley rats. Behav. Brain Res., 44, 43-51.
4. Burgess, L.H. and Handa, R.J. (1993): Hormonal regulation of androgen receptor mRNA in the brain and anterior pituitary gland of the male rat. Brain Res. Mol. Brain Res., 19, 31-38.
5. Clemens, L.G., Gladue, B.A. and Coniglo, L.P. (1978): Prenatal endogenous androgenic influences on masculine sexual behavior and genital morphology in male and female rats. Horm. Behav., 10, 40-53.
6. Dahl, E. (1976): The ultrastructure of the accessory sex organs of the male rat. XI. Nuclear alterations of prostatic epithelial cells induced by castration. Cell Tissue Res., 171, 285-96.
7. Dohler, K.D., Coquelin, A., Davis, F. and Hines, M. (1982): Differentiation of the sexually dimorphic nucleus in the preoptic area of the rat brain is determined by the perinatal hormone environment. Neurosci. Lett., 33, 295-298.
8. Dohler, K.D., Coquekin, F., Hines, M., Shryne, J.E. and Gorski, R.A. (1984): Pre- and postnatal influence of testosterone propionate and diethylstilbestrol on differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats. Brain Res., 302, 291-295.
9. Dunnett, C.W. (1955): A multiple comparison for comparing several treatments with a control. J. Am. Stat. Assoc., 50, 1096-1121.
10. Fang, S., Anderson, K.M. and Liao, S. (1969): Receptor protein for androgen. On the role of specific proteins in selective retention of 17-beta-hydroxy-5-alpha-androstan-3-one by rat ventral prostate in vivo and in vitro. J. Biol. Chem., 244, 6584-6595.
11. Frye, C.A. (1995): Estrus-associated decrements in a water maze task are limited to acquisition. Physiol. Behav., 57, 5-14.
12. Gladue, B.A. and Clemens, L.G. (1978): Androgenic influences on feminine sexual behavior in male and female rats: Defeminization blocked by prenatal androgen treatment. Endocrinology, 103, 1702-1709.
13. Gladue, B.A. and Clemens, L.G. (1980): Flutamide inhibits testosterone-induced masculine sexual behavior in male and female rats. Endocrinology, 106, 1917-1922.
14. Gladue, B.A. and Clemens, L.G. (1982): Development of feminine sexual behavior in the rat: androgenic and temporal influences. Physiol. Behav., 29, 263-267.
15. Goto, K., Koizumi, K., Takaori, H., Fujii, Y., Furuyama, Y., Saika, O., Suzuki, H., Saito, K. and Suzuki, K. (2004): Effects of flutamide on sex maturation and sexual behavior of offspring born to female rats treated during late pregnancy. J. Toxcol. Sci., 29, 517-534.
16. Imai, K., Watanabe, K., Takahashi, O., Shimizu, N., Nakata, S., Kawashima, K., Suzuki, T. and Yamanaka, H. (1990): [A study of the androgenic activity of anti-androgen] in Japanese. Nippon Naibunpi. Gakkai Zasshi, 66, 597-606.
17. Joseph, R., Hess, E. and Birecree, S. (1978): Effects of hormone manipulations and exploration on sex differences in maze learning. Behav. Biology, 24, 364-377.
18. Kaya, H., Hany, J., Fastabend, A., Roth-Harer, A., Winneke, G. and Lilienthal, H. (2002): Effects of maternal exposure to reconstituted mixture of polychlorinated biphenyls on sex-dependent behaviors and steroid hormone concentrations in rats: dose-response relationship. Toxicol. Appl. Pharmacol., 178, 71-81.
19. Kelce, W.R., Lambright, C.R., Gray, L.E. and Roberts, K.P. (1997): Vinclozolin and pp′-DDE alter androgen-dependent gene expression: In vivo confirmation of an androgen receptor-mediated mechanism. Toxicol. Appl. Pharmacol., 142, 192-200.
20. Kerr, J.E., Allore, R.J., Beck, S.G. and Handa, R.J. (1995): Distribution and hormonal regulation of androgen receptor (AR) and AR messenger ribonucleic acid in the rat hippocampus. Endocrinology, 136, 3213-3221.
21. Kumar, V.L., Majumder, P.K. and Kumar, V. (1997): Androgen deprivation causes up-regulation of androgen receptor transcript in the rat prostate. Mol. Cell Biochem., 171, 133-138.
22. Kumar, V.L., Majumder, P.K. and Kumar, V. (2002): In vivo modulation of androgen receptor by androgens. Asian J. Androl., 4, 229-231.
23. Lephart, E.D. (1996): A review of brain aromatase cytochrome P450. Brain Research Review, 22, 1-26.
24. Lephart, E.D., Call, S.B., Rhees, R.W., Jacobson, N.A., Weber, K.S., Bledsoe, J. and Teuscher, C. (2001): Neuroendocrine regulation of sexually dimorphic brain structure and associate sexual behavior in male rats is genetically controlled. Biol. Reprod., 64, 571-578.
25. Lund, T.D., Salyer, D.L., Fleming, D.E. and Lephart, E.D. (2000): Pre- and postnatal testosterone and flutamide effects on sexually dimorphic nuclei of the rat hypothalamus. Dev. Brain Res., 120, 261-266.
26. MacLusky, N.J. and Naftolin, F. (1981): Sexual differentiation of the central nervous system. Science, 211, 1294-1303.
27. McAbee, M.D. and Doncarlos, L.L. (1999): Estrogen, but not androgens, regulates androgen receptor messenger ribonucleic acid expression in the developing male rat forebrain. Endocrinology, 140, 3674-3681.
28. Mooradian, A.D., Morley, J.E. and Korenman, S.G., (1987): Biological actions androgens. Endocr. Rev., 8, 1-28.
29. Nagao, T. (2003): Physiological effects of diethylstilbestrol (abstract in Japanese). In Endocrine Disruptor Substances special symposium., pp 41-45.
30. Ohe, E. (1994): [Effects of aromatase inhibitor on sexual differentiation of SDN-POA in rats] in Japanese. Nippon Sanka Fujinka Gakkai Zasshi, 46, 227-234.
31. Quarmby, V.E., Yarbrough, W.G., Lubahn, D.B., French, F.S. and Wilson, E.M. (1990): Autologous down-regulation of androgen receptor messenger ribonucleic acid. Mol. Endocrinol., 4, 22-28.
32. Rhees, R.W., Shryne, J.E. and Gorski, R.A. (1990): Onset of the hormone-sensitive perinatal period for sexual differentiation of the sexually dimorphic nucleus of the preoptic area in the female rats. J. Neurobiology, 21, 781-786.
33. Roof, R.L. (1993): Neonatal exogenous testosterone modifies sex difference in radial arm and Morris water maze performance in prepubescent and adult rats. Behav. Brain Res., 53, 1-10.
34. Schindler, C.W. and Carmona, G.N. (2002): Effect of dopamine agonists and antagonists on locomotor activity in male and female rats. Pharmacol. Biochem. Behav., 72, 857-863.
35. Shan, L.X., Rodriguez, M.C. and Janne, O.A. (1990): Regulation of androgen receptor protein and mRNA concentrations by androgens in rat ventral prostate and seminal vesicles and in human hepatoma cells. Mol. Endocrinology, 4, 1636-1646.
36. Singh, S.M., Gauthier, S. and Labrie, F. (2000): Androgen receptor antagonists (antiandrogens): Structure-activity relationships. Curr. Med. Chem., 7, 211-247.
37. Sodersten, P., Gray, G., Damassa, D.A., Smith, E.R. and Davidson, J.M. (1975): Effects of a non-steroidal antiandrogen on sexual behavior and pituitary-gonadal function in the male rat. Endocrinology, 97, 1468-1475.
38. Steel, R.G.D.(1959): A multiple comparison rank sum test: Treatments versus control. Biometrics, 15, 560-572.
39. Steinsapir, J., Mora, G. and Muldoon, T.G. (1991): Effects of steroidal and non-steroidal antiandrogens on the androgen binding properties of the rat ventral prostate androgen receptor. Biochim. Biophys. Acta., 1094, 103-112.
40. Tarttelin, M.F. and Gorski, R.A. (1991): Postnatal influence of diethylstilbestrol on the differentiation of the sexually dimorphic nucleus in the rat is as effective as perinatal treatment. Brain Res., 456, 271-274.
41. Vagell, M.E. and McGinnis, M.Y. (1998): The role of gonadal steroid receptor activation in the restoration of sociosexual behavior in adult male rats. Horm. Behav., 33, 163-179.
42. Vega Matuszczyk, J.V. and Larsson, K. (1995): Sexual preference and feminine and masculine sexual behavior of male rats prenatally exposed to antiandrogen or antiestrogen. Horm. Behav., 29, 191-206.
43. Williams, C.L., Barnett, A.M. and Meck, W.H. (1990): Organizational effects of early gonadal secretions on sexual differentiation in spatial memory. Behav. Neurosci., 104, 84-97.
44. Yamada, T., Kunimatsu, T., Sako, H., Yabushita, S., Sukata, T., Okuno, Y. and Matsuo, M. (2000): Comparative evaluation of a 5-day Hershberger assay utilizing mature male rats and a pubertal male for detection of flutamide's antiandrogenic activity. Toxicol. Sci., 53, 289-296.
45. Yoshimura, I. (2003): In "Statistical Analysis of Toxicological Data", pp. 26-42, Scientist, Tokyo (in Japanese).
46. Zimmerberg, B. and Farley, M.J. (1993): Sex differences in anxiety behavior in rats: Role of gonadal hormones. Physiol. Behav., 54, 1119-1124.